1. Field of the Invention
The present disclosure relates to treatments of cancers. Specifically, the present disclosure relates to novel bi-specific antibodies and their uses for suppressing the growth or metastasis of cancers; and tracking the development of cancers.
2. Description of Related Art
Covalent attachment of poly(ethylene glycol) (PEGylation) to substances such as proteins, peptides, and nanoparticles (NPs) (e.g., liposomes, micelles, and the like) can increase drug bioavailability, enhance blood circulation half-life and hinder capture by the reticuloendothelial system (RES). These favorable attributes have led to the widespread use of PEGylation in the development of NPs including those available in clinical use, such as liposomal doxorubicin (Caelyx) for the treatment of ovarian and breast carcinomas and Kaposi's sarcoma and Genexol-PM® (Paclitaxel-loaded PEG-PLA micelles), approved for metastatic breast cancer, non-small cell lung cancer and ovarian cancer in South Korea. PEGylated nanoparticles (PEG-NPs) are highly regarded as the second generation of drug delivery systems and the mainstream of therapeutic or imaging agents.
PEGylated substances, particularly, PEG-NPs can accumulate in tumors due to the enhanced permeability and retention (EPR) effect caused by the abnormal structure of endothelial cells in tumors. PEG-NPs, however, often accumulate near tumors but do not penetrate into the tumor mass, and some drugs cannot easily diffuse from PEG-NPs to cancer cells. Therefore, several studies reported that chemical conjugation of antibodies to PEG-NPs increases specific targeting and intracellular uptake which improves therapeutic efficacy and the sensitivity of imaging. However, chemically linking antibodies to PEG-NPs is difficult to achieve. Most functional groups (e.g., amino, carboxyl, thiol groups) are abundant in ligands, which may cause loss of antibody function, or result in heterogeneous orientation of the antibody, thereby rendering it difficult to obtain a reproducible product after chemical conjugation. Further, chemical conjugation may also alter the structure of nano-carriers and encapsulated drugs. These problems limit the clinical applicability of targeted NPs.
In view of the foregoing, there exist in the related art, a need for an improved way of targeting PEGylated substances (e.g., PEG-NPs), which is reproducible and easy to use.